Xinshubao tablet ameliorates myocardial injury against heart failure via the DCN/PPARα/PGC-1α/P300 pathway.
作者: Qingqing Cai ; Yu Li ; Yi Zhang ; He Xu ; Lifang Wang ; Jixiang Tian ; Fangbo Zhang ; Hongjun Yang
Heart failure (HF) is a complex clinical syndrome with impaired ventricular ability due to structural or functional cardiac disorders. A traditional Chinese formula named Xinshubao tablet (XSB) is reported to protect cardiomyocytes and decrease the risk of HF clinically; however, the underlying mechanism of XSB on decreasing HF risk is not elucidated yet. Therefore, our study aimed to investigate the therapeutic efficacy and underlying mechanism of XSB by using HF model rats and H9c2 cells with oxygen glucose deprivation. Echocardiographic and pathological features of animal experiment showed that XSB treatment effectively improved cardiac function and ameliorated myocardial injury after 4 weeks of treatment. Cellular experiments indicated that XSB pretreatment significantly inhibited apoptosis and increased mitochondrial energy metabolism. Furthermore, in vivo and in vitro experiments both demonstrated that XSB suppressed oxidative stress and inflammatory response. Our results further revealed that the potential protective mechanism of XSB was closely associated with the DCN/PPARα/PGC-1α/P300 signaling pathway. Our findings provide novel mechanistic insights for HF treatment and a pharmacological basis for the therapeutic application of XSB against cardiovascular disorders.
Study on the Anti-Inflammatory Effect and Mechanism of Yuxuebi Tablet Based on Network Pharmacology
Yuxuebi tablet (YXB) is a Chinese patent medicine with the effect of activating blood circulation and dissipating blood stasis and has been used to treat "Bi" syndrome in China. The aim of this study was to reveal its anti-inflammatory efficacy and mechanism. A carrageenan-induced inflammation mouse model was established to demonstrate the anti-inflammatory efficacy of YXB by detecting the paw swelling degree and inflammatory cell infiltration in paws. The active chemical ingredients and anti-inflammatory targets of YXB were obtained through network pharmacology analysis. Finally, the core anti-inflammatory targets of YXB were determined by the ELISA method and western blot. YXB significantly reduced the paw swelling degree and inflammatory cell infiltration in paws. A total of 120 key active components included in YXB interacted with 56 core inflammatory targets (such as TNF, IL1B, IL6, PTGS2, RELA, MAPK1, MAPK8, and MAPK14), mainly involving in the TNF signaling pathway, Toll-like receptor signaling pathway, NF-kappaB signaling pathway, and NOD-like receptor signaling pathway. Further studies in vivo found that YXB reduced the levels of TNF-α, IL-1β, and IL-6 in serum and inhibited the expression of COX-2 and the phosphorylation levels of NF-κB p65, JNK, and p38 protein in paws. Taken together, YXB had a good anti-inflammatory effect, which might be related to inhibiting the phosphorylation of NF-κB, JUN, and p38 and the decrease of COX-2 expression and the levels of inflammatory factors.
2022-08-08·Journal of ethnopharmacology
Anti-angiogenic effect of YuXueBi tablet in experimental rheumatoid arthritis by suppressing LOX/Ras/Raf-1 signaling.
作者: Xiaohui Su ; Bei Yuan ; Xueying Tao ; Wanyi Guo ; Xia Mao ; Anguo Wu ; Qian Wang ; Chunfang Liu ; Yanqiong Zhang ; Xiangying Kong ; Lan Han ; Na Lin
A Chinese patent medicine derived from a classical traditional Chinese medicine formula, Yu-Xue-Bi tablet (YXB) is widely used in the clinic to treat rheumatoid arthritis (RA). During the progression of RA, angiogenesis plays a central role in fostering the production of inflammatory cells, leading to synovial hyperplasia and bone destruction. However, whether YXB attenuates the angiogenesis during RA progression remains to be defined.
AIM OF THE STUDY:
We aimed to evaluate the anti-angiogenic activity of YXB and explore its mechanism of action in collagen-induced arthritis (CIA) rats and VEGF-induced HUVECs.
MATERIALS AND METHODS:
Transcriptional regulatory network analysis and a network pharmacology approach were employed to explore mechanism of YXB in RA angiogenesis. The antiarthritic effect of YXB was evaluated by determining the arthritis incidence, and score, and by micro-CT analysis. The anti-angiogenic effect of YXB in vivo was assessed by histological and immunohistochemical analyses. The anti-angiogenic effect of YXB in vitro was assessed by wound healing, Transwell migration, Transwell invasion, and tube formation assays. Western-blotting and immunohistochemical analysis were employed to explore the molecular mechanisms of YXB.
YXB reduced disease severity and ameliorated pathological features in CIA rats. YXB markedly decreased bone destruction and synovial angiogenesis. Consistently, we also demonstrated that YXB effectively suppressed angiogenesis marker CD31 and VEGF expression. In vitro, YXB effectively inhibited HUVEC migration, invasion, and tube formation. Following the identification of transcriptional expression profiles, "YXB putative targets-known RA-related genes-genes associated with the therapeutic effect of YXB" interaction network was constructed and analyzed. After that, the LOX/Ras/Raf-1 signaling axis, which is involved in RA angiogenesis, was identified as one of the candidate mechanisms of YXB against RA. Experimentally, YXB dose-dependently decreased the expression levels of LOX, Ras, and Raf-1, as well as the phosphorylation of MEK and ERK in CIA rats, and these effects were better than the inhibitory effects of methotrexate (MTX), an FDA approved drug used for some autoimmune diseases such as RA. In addition, YXB may function as a potent angiogenesis inhibitor and significantly suppress the VEGF-induced activation of LOX/Ras/Raf-1 signaling in vitro.
We provide evidence that YXB may decrease the disease severity of RA and reduce bone erosion by suppressing angiogenesis via inhibition of LOX/Ras/Raf-1 signaling.